Issue 41, 2023

GSH-activatable camptothecin prodrug-loaded gold nanostars coated with hyaluronic acid for targeted breast cancer therapy via multiple radiosensitization strategies

Abstract

Breast cancer has overtaken lung cancer to rank as the top malignant tumor in terms of incidence. Herein, a gold nanostar (denoted as AuNS) is used for loading disulfide-coupled camptothecin-fluorophore prodrugs (denoted as CPT-SS-FL) to form a nanocomposite of AuNS@CPT-SS-FL (denoted as AS), which, in turn, is further encapsulated with hyaluronic acid (HA) to give the final nanoplatform of AuNS@CPT-SS-FL@HA (denoted as ASH). ASH effectively carries the prodrug and targets the CD44 receptor on the surface of tumor cells. The endogenously overexpressed glutathione (GSH) in tumor cells breaks the disulfide bond to activate the prodrug and release the radiosensitizer drug camptothecin (CPT) and the fluorescence imaging reagent rhodamine derivative as a fluorophore (FL). The released FL can track the precise release position of the radiosensitizer camptothecin in tumor cells in real time. The AuNS has strong X-ray absorption and deposition ability due to the high atomic coefficient of elemental Au (Z = 79). At the same time, the AuNS can alleviate the tumor microenvironment (TME) hypoxia through its mild photothermal therapy (PTT). Therefore, through the multiple radiosensitizing effects of GSH depletion, the high atomic coefficient of Au, and hypoxia alleviation, accompanied by the radiosensitizer camptothecin, the designed ASH nanoplatform can effectively induce strong immunogenic cell death (ICD) at the tumor site via radiosensitizing therapy combined with PTT. This work provides a new way of constructing a structurally compact and highly functionalized hierarchical system toward efficient breast cancer treatment through ameliorating the TME with multiple modalities.

Graphical abstract: GSH-activatable camptothecin prodrug-loaded gold nanostars coated with hyaluronic acid for targeted breast cancer therapy via multiple radiosensitization strategies

Supplementary files

Article information

Article type
Paper
Submitted
28 Agd 2023
Accepted
30 Leq 2023
First published
05 Way 2023

J. Mater. Chem. B, 2023,11, 9894-9911

GSH-activatable camptothecin prodrug-loaded gold nanostars coated with hyaluronic acid for targeted breast cancer therapy via multiple radiosensitization strategies

Y. Hou, B. Sun, R. Li, W. Meng, W. Zhang, N. Jia, M. Chen, J. Chen and X. Tang, J. Mater. Chem. B, 2023, 11, 9894 DOI: 10.1039/D3TB00965C

To request permission to reproduce material from this article, please go to the Copyright Clearance Center request page.

If you are an author contributing to an RSC publication, you do not need to request permission provided correct acknowledgement is given.

If you are the author of this article, you do not need to request permission to reproduce figures and diagrams provided correct acknowledgement is given. If you want to reproduce the whole article in a third-party publication (excluding your thesis/dissertation for which permission is not required) please go to the Copyright Clearance Center request page.

Read more about how to correctly acknowledge RSC content.

Social activity

Spotlight

Advertisements